(1) Background: Standard-of-care lifestyle interventions show insufficient effectiveness for the prevention and treatment of excess weight and its associated cardiometabolic health concerns in adolescents, necessitating more targeted preventative approaches. Anxiety symptoms are common among adolescents, especially girls at risk for excess weight gain, and have been implicated in the onset and maintenance of disinhibited eating. Thus, decreasing elevated anxiety in this subset of adolescent girls may offer a targeted approach to mitigating disinhibited eating and excess weight gain to prevent future cardiometabolic health problems. (2) Methods: The current paper describes the protocol for a multisite pilot and feasibility randomized controlled trial of group cognitive behavioral therapy (CBT) and group interpersonal psychotherapy (IPT) in N = 40 adolescent girls (age 12–17 years) with elevated anxiety symptoms and body mass index (BMI; kg/m²) ≥ 75th percentile for age/sex. (3) Results: Primary outcomes are multisite feasibility of recruitment, protocol procedures, and data collection, intervention fidelity, retention at follow-ups, and acceptability of interventions and study participation. (4) Conclusions: Findings will inform the protocol for a future fully-powered multisite randomized controlled trial to compare CBT and IPT efficacy for reducing excess weight gain and preventing adverse cardiometabolic trajectories, as well as to evaluate theoretically-informed treatment moderators and mediators.